Tolvaptan For Worsening Outpatient Heart Failure: Role of Copeptin In Identifying Responders (TROUPER)

May 3, 2022 updated by: University of North Carolina, Chapel Hill

Tolvaptan Treatment to Reverse Worsening Outpatient Heart Failure: Possible Role of Copeptin In Identifying Responders (TROUPER)

Patients who present to clinic or in the outpatient setting with worsening heart failure represent a unique opportunity for novel approaches to decongestion (removing fluid) that may more rapidly improve fluid status and symptoms as well as reduce the risk of hospitalization.

In these patients with less severe congestion (fluid overload), combining the vasopressin antagonist tolvaptan with loop diuretics (or fluid pills like furosemide/bumetanide/torsemide) may represent a more effective strategy for decongestion. In addition, looking at patients' copeptin levels may help identify those who are more likely to respond to tolvaptan.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will be a randomized, double blind, positive control, multi-center clinical trial enrolling patients who present in the outpatient setting with signs and symptoms consistent with worsening congestive heart failure. The sample size for the study is 40 patients. Candidates for the study will be identified by screening outpatients presenting with worsening heart failure.

Patients who qualify for the study will be enrolled within 24 hours of identification. Patients will be randomized in a 1:1 fashion to one of two treatment arms:

  • Augmentation of current daily dose of oral loop diuretic + 30 mg of oral Tolvaptan daily
  • Augmentation of current daily dose of oral loop diuretic + placebo of oral Tolvaptan daily

Patients will initiate study medication in a hospital setting and will be observed for a period of time that will depend upon their baseline serum sodium and response to study drug. In most cases patients will be observed for 8 hours. Following this observational period, patients will leave the hospital setting and the remainder of the study will consist of follow-up by outpatient visits or by telephone. All patients will have Day 30 follow up phone contact for assessment of vital status, adverse events and morbidity during this period.

The primary objective of this study will be to compare the effects of oral tolvaptan plus augmented loop diuretic versus augmented loop diuretic on short term changes in body weight with and without stratification for baseline copeptin.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ≥ 18 years of age

  • Presenting to clinic with worsening heart failure due congestion (fluid overload) Patient reported worsening fluid overload based on perception of edema and/or weight gain With at least one of the following symptoms

    • Worsening dyspnea on exertion or fatigue
    • Worsening orthopnea or paroxysmal nocturnal dyspnea (PND)
    • Perception of abdominal and/or lower extremity edema
    • Early satiety and/or decreased appetite And at least one of the following signs
    • Lower extremity edema
    • Ascites
    • Elevated jugular venous distension (JVD)
    • Pulmonary rales
  • Daily oral dose of loop diuretic
  • Prior history of heart failure with this diagnosis for at least 1 month with preserved or reduced left ventricular ejection fraction
  • Signed informed consent

Exclusion Criteria:

  • Patients with symptomatic hyponatremia will be excluded from the study.
  • Patients with severe hyponatremia, defined as serum sodium < 125 milliequivalents per Liter (mEq/L) at the time of screening, will be excluded regardless of whether they are symptomatic or not.
  • Patients with the following predisposing factors for osmotic demyelinating syndrome (ODS), assessed by the study investigator judgment, will be excluded: chronic alcoholism at the time of study, severe liver disease, marked malnutrition, and risk for chronic hypoxia.
  • Patients currently undergoing renal replacement therapy
  • Planned hospitalization for acute heart failure
  • History of primary significant liver disease or acute hepatic failure, as defined by the investigator
  • Hemodynamically significant arrhythmias
  • Acute coronary syndrome (ACS) or acute myocardial infarction within 4 weeks prior to study entry
  • Active myocarditis
  • Hypertrophic obstructive, restrictive, or constrictive cardiomyopathy
  • Severe stenotic valvular disease amendable to surgical treatment
  • Complex congenital heart disease
  • Constrictive pericarditis
  • Clinical evidence of digoxin toxicity

  • History of adverse reaction or clinical contraindication to tolvaptan

    • Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors
    • Inability of patient to sense and/or respond to thirst
    • History of hypersensitivity to tolvaptan
    • Patient is anuric
  • Enrollment or planned enrollment in another randomized clinical trial during the study period
  • Pregnant or breast-feeding
  • Inability to comply with planned study procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tolvaptan
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Drug: tolvaptan
Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
Other Names:
  • Samsca
Placebo Comparator: Placebo
Augmentation of current dose of loop diuretic
Other: Placebo
Placebo for tolvaptan

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Body Weight at 48 Hours
Time Frame: Baseline, Day 3 (48 hours)
The primary endpoint for the study will be change in body weight between patients randomized to tolvaptan versus placebo from baseline to 48 hours
Baseline, Day 3 (48 hours)
Change in Body Weight at 48 Hours Stratified by Copeptin
Time Frame: Baseline, Day 3 (48 hours)
The primary endpoint for the study will be change in body weight between patients randomized to tolvaptan versus placebo from baseline to 48 hours with stratification for baseline copeptin level
Baseline, Day 3 (48 hours)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in Visual Analog Scale - Patient Dyspnea
Time Frame: Baseline, Day 3 (48 hours)

Changes in patient reported dyspnea scale from baseline to 48 hours based on the visual analog scale.

Visual Analog Scale (VAS) - Patient Dyspnea has a minimum value of 0 and a maximum value of 100. Higher scores mean a better outcome.
Baseline, Day 3 (48 hours)
Change in Loop Diuretic Dose (Furosemide Milligram Equivalents) at 48 Hours
Time Frame: Day 3 (48 hours)
Change in loop diuretic dose at 48 hours where doses of loop diuretic are expressed as furosemide milligram equivalents based on standard conversions of bumetanide and torsemide doses to milligram equivalents of furosemide. The formula for the conversion of doses of loop diuretics were standardized to milligram equivalents of furosemide based on 40 milligrams of furosemide for each 1 milligram of bumetanide and 2 milligrams of furosemide for each 1 milligram of torsemide.
Day 3 (48 hours)
Number of Participants With a Decrease in Loop Diuretic Dosing at 48 Hours
Time Frame: Day 3 (48 hours)
Number of participants with a decrease in loop diuretic diuretic dosing at 48 hours in the Tolvaptan group and the Placebo group.
Day 3 (48 hours)
Change in Loop Diuretic Score Defined Based on Change in Loop Diuretic Use
Time Frame: Day 3 (48 hours)
Change in loop diuretic score defined by change in loop diuretic use at Visit 2. The change in loop diuretic score endpoint was calculated as follows: patients having an increase in loop diuretic use at Visit 2 were given a score of 2, patients with no change a score of 0, and patients with a decrease in loop use at Visit 2 were given a score of -1. Increases in loop diuretic use were given a higher weighting to account for their reflection of treatment failure.
Day 3 (48 hours)
Change in Body Weight at Day 8
Time Frame: Baseline, 8 days
Change in body weight at 8 days will be analyzed in a similar fashion to the change in body weight at 48 hours
Baseline, 8 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of North Carolina, Chapel Hill

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Otsuka America Pharmaceutical

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kirkwood F Adams, MD, University of North Carolina, Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 13, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 13, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 19, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 5, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15-0472

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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